Effect of different G protein-coupled receptor kinases on phosphorylation and desensitization of the alpha1B-adrenergic receptor.

Détails

ID Serval
serval:BIB_B4953C3AF67A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Effect of different G protein-coupled receptor kinases on phosphorylation and desensitization of the alpha1B-adrenergic receptor.
Périodique
Journal of Biological Chemistry
Auteur(s)
Diviani D., Lattion A.L., Larbi N., Kunapuli P., Pronin A., Benovic J.L., Cotecchia S.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
1996
Volume
271
Numéro
9
Pages
5049-5058
Langue
anglais
Résumé
The alpha1B-adrenergic receptor (alpha1BAR), its truncated mutant T368, different G protein-coupled receptor kinases (GRK) and arrestin proteins were transiently expressed in COS-7 or HEK293 cells alone and/or in various combinations. Coexpression of beta-adrenergic receptor kinase (betaARK) 1 (GRK2) or 2 (GRK3) could increase epinephrine-induced phosphorylation of the wild type alpha1BAR above basal as compared to that of the receptor expressed alone. On the other hand, overexpression of the dominant negative betaARK (K220R) mutant impaired agonist-induced phosphorylation of the receptor. Overexpression of GRK6 could also increase epinephrine-induced phosphorylation of the receptor, whereas GRK5 enhanced basal but not agonist-induced phosphorylation of the alpha1BAR. Increasing coexpression of betaARK1 or betaARK2 resulted in the progressive attenuation of the alpha1BAR-mediated response on polyphosphoinositide (PI) hydrolysis. However, coexpression of betaARK1 or 2 at low levels did not significantly impair the PI response mediated by the truncated alpha1BAR mutant T368, lacking the C terminus, which is involved in agonist-induced desensitization and phosphorylation of the receptor. Similar attenuation of the receptor-mediated PI response was also observed for the wild type alpha1BAR, but not for its truncated mutant, when the receptor was coexpressed with beta-arrestin 1 or beta-arrestin 2. Despite their pronounced effect on phosphorylation of the alpha1BAR, overexpression of GRK5 or GRK6 did not affect the receptor-mediated response. In conclusion, our results provide the first evidence that betaARK1 and 2 as well as arrestin proteins might be involved in agonist-induced regulation of the alpha1BAR. They also identify the alpha1BAR as a potential phosphorylation substrate of GRK5 and GRK6. However, the physiological implications of GRK5- and GRK6-mediated phosphorylation of the alpha1BAR remain to be elucidated.
Mots-clé
Adrenergic beta-Agonists/pharmacology, Animals, Antigens/biosynthesis, Antigens/isolation & purification, Arrestins, Blotting, Western, Cattle, Cell Line, Cercopithecus aethiops, Cyclic AMP-Dependent Protein Kinases/biosynthesis, Cyclic AMP-Dependent Protein Kinases/metabolism, Epinephrine/pharmacology, Eye Proteins/biosynthesis, Eye Proteins/isolation & purification, GTP-Binding Proteins/biosynthesis, GTP-Binding Proteins/isolation & purification, Gene Expression, Humans, Kidney, Kinetics, Mutagenesis, Phosphatidylinositols/metabolism, Phosphorylation, Receptor Protein-Tyrosine Kinases/biosynthesis, Receptor Protein-Tyrosine Kinases/isolation & purification, Receptors, Adrenergic, alpha-1/metabolism, Receptors, Adrenergic, alpha-1/physiology, Recombinant Proteins/biosynthesis, Recombinant Proteins/isolation & purification, Transfection, beta-Adrenergic Receptor Kinases
Pubmed
Web of science
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 15:23
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